免疫球蛋白GN-糖基化与中心性肥胖的关联研究

Association between N-glycans of immunoglobulin G and central obesity

目的探索中国人群中免疫球蛋白G（IgG）糖基化与中心性肥胖的关联。方法采用横断面研究，整群抽样法于2012年4至7N在北京市西城区某社区，纳人517人作为研究对象，测量身高、体重、腰围、臀围，并采集血液样本，提取纯化血浆IgG，采用超高压液相色谱法进行IgG糖基组学检测。以腰臀比定义中心性肥胖，男性腰臀比〉O．90，女性腰臀比〉0．80划分为中心性肥胖组；男性腰臀比≤0．90，女性腰臀比≤0．80划分为正常组。腰臀比和糖基峰的关联以标准化回归系数呈现，P〈0．05为差异有统计学意义。结果517名居民平均年龄（47．81±5．58）岁，男性164人（31．70％）。中心性肥胖组205例（39．65％），正常组312人（60．35％），中心性肥胖组年龄（49．21±5．70）岁高于正常组的（46．89±5．30）岁，差异有统计学意义（t=-4．73，P=0．001）。男性中心性肥胖62例（37．80％），女性中心性肥胖143例（40．50％），差异无统计学意义（X2=0．34，P=0．558）。IgG糖基组学检测得到24个不同的糖基峰结构，由于糖基峰3和20受到污染和结构不明，被排除分析，余下的22个糖基峰中，GP4、GP8、GPl4、GPl8含量较多，4个峰的含量约占所有峰的50％。腰臀比与糖基峰中核心岩藻糖（GPl0）呈正相关（b＇=0．076，P=0．024），而与末端半乳糖（GPl2）、末端唾液酸（GPl7、GP22）呈负相关（b＇=-0．076、-0．081、-0．080，P均〈0．05）。中心性肥胖组的GPl2、GPl7、GP22含量均低于正常组，差异均有统计学意义（P=0．001、0．004、0．033）。结论中心性肥胖人群IgG末端半乳糖和末端唾液酸化水平较低及核心岩藻糖的水平较高。

Objective To explore the association between immunoglobulin G （IgG） glycosylation and centra｜ obesity in a Chinese population. Methods We recruited 517 Chinese individuals from a community-based cohort in the Xicheng District, Beijing, China. The height, weight, waist circumference, and hip circumference were measured, and blood samples were collected. Plasma IgG N-glycome was determined using hydrophilic interaction liquid chromatography （HILIC）. Central obesity was determined using the waist-to-hip ratio （WHR）. Men and women with a WHR〉0.90 and 〉0.80, respectively were assigned to the central obese group, and those with a WHR ≤0.90 （men） and ≤0.80 （women） were assigned to the normal group. The correlation between WHR and glycosylation was determined using the standardized regression coefficient, and P〈0.05 was considered statistically significant. Results The study included 517 participants, with an average age of （47.81＋5.58） years （range： 27-68 years）, and 164 （31.70%） of them were men. The central obese and normal groups included 205 （39.65%） and 312 （60.35%） participants, respectively. The average age for the central obese group （49.21_＋5.70） years was higher than that for the normal group （46.89±5.30） years, and the difference was statistically significant （t=-4.73, P=0.001）. The two groups showed no significant differences in the sex of the participants （X2=0.34, P=0.558）. Twenty-four N-glycan traits （GP1-GP24） were directly measured, and because of the high variability among the repeated measurements and the unknown structures, GP3 and GP20 were excluded from the analysis. The peak contents for GP4, GP8, GP14, and GP18 were higher than the others and accounted for about 50% of all the peak contents. IgG GP10 （b＇=0.076, P=0.024） positively correlated with WHR, whereas IgG GP12, GP17, GP22 negatively correlated with WHR （b＇=-0.076, -0.081, -0.080, all P〈0.05）. Additionally, the IgG GP12, GP17, and GP22 （P=0.O01, 0.004 and 0.033, respectively） were significantly lower in the participants of the central obese group, compared to those of the normal group. Conclusion The loss of galactose and sialic acid, as well as the addition of fucose to IgG N-glycan, correlate with increased WHR.